Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation.

Abstract

BACKGROUND:

cblC disease is a cause of hemolytic uremic syndrome (HUS), which has been primarily described in neonates and infants with severe renal and neurological lesions.

PATIENTS:

Two sisters aged 6 and 8.5 years presented with a latent hemolytic process characterized by undetectable or low plasma haptoglobin, respectively, associated with renal failure and gross proteinuria. Renal biopsies performed in both patients found typical findings of thrombotic microangiopathy suggesting the diagnosis of HUS. Both patients were free of neurologic signs.

RESULTS:

Biochemical investigations found a cobalamin processing deficiency of the cblC type. Search for additional factors susceptible to worsen endothelial damage revealed homozygosity 677C--> T mutation in the methylenetetrahydrofolate reductase gene as well as heterozygosity for a 3254T--> C mutation in factor H in the patient with the most severe clinical presentation. Long-term subcutaneous administration of hydroxocobalamin in combination with oral betaine and folic acid resulted in clinical and biological improvement in both patients.

CONCLUSION:

cblC disease may be a cause of chronic HUS with delayed onset in childhood. Superimposed mutation of factor H gene might influence clinical severity.

• Authors: Vincent Guigonis, Véronique Frémeaux-Bacchi, Stéphane Giraudier, Rémi Favier, Didier Borderie, Ziad Massy, Béatrice Mougenot, David S Rosenblatt, Georges Deschênes
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 45 Issue 3 Pg. 588-95 (Mar 2005) ISSN: 1523-6838 [Electronic] United States
• PMID: 15754282 (Publication Type: Case Reports, Journal Article)

Chemical References

• CFH protein, human
• Haptoglobins
• Proto-Oncogene Proteins
• betaine citrate
• Betaine
• Complement Factor H
• Folic Acid
• Methylenetetrahydrofolate Reductase (NADPH2)
• Proto-Oncogene Proteins c-cbl
• CBLC protein, human
• Vitamin B 12
• Hydroxocobalamin

Topics

• Anemia (etiology)
• Betaine (analogs & derivatives, therapeutic use)
• Child
• Combined Modality Therapy
• Complement Factor H (genetics)
• Drug Therapy, Combination
• Endothelium, Vascular (pathology)
• Female
• Folic Acid (therapeutic use)
• Genetic Predisposition to Disease
• Genotype
• Haptoglobins (deficiency)
• Hemolytic-Uremic Syndrome (drug therapy, genetics, therapy)
• Humans
• Hydroxocobalamin (therapeutic use)
• Hypertension (etiology)
• Kidney (blood supply, pathology)
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Mutation, Missense
• Nephrotic Syndrome (etiology)
• Plasma Exchange
• Point Mutation
• Proteinuria (etiology)
• Proto-Oncogene Proteins (deficiency, genetics)
• Proto-Oncogene Proteins c-cbl
• Renal Dialysis
• Vitamin B 12 (metabolism)